In this paper, we consider the domain of executive functions (EFs) and their possible role in developmental psychopathologies. We first consider general theoretical and measurement issues involved in studying EFs and then review studies of EFs in four developmental psychopathologies: attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), autism, and Tourette syndrome (TS). Our review reveals that EF deficits are consistently found in both ADHD and autism but not in CD (without ADHD) or in TS. Moreover, both the severity and profile of EF deficits appears to differ across ADHD and autism. Molar EF deficits are more severe in the latter than the former. In the few studies of more specific EF tasks, there are impairments in motor inhibition in ADHD but not in autism, whereas there are impairments in verbal working memory in autism but not ADHD. We close with a discussion of implications for future research.

Executive Functions and Developmental Psychopathology

Sleep function and synaptic homeostasis.

Researchers have wondered how the brain creates emotions since the early days of psychological science. With a surge of studies in affective neuroscience in recent decades, scientists are poised to answer this question. In this target article, we present a meta-analytic summary of the neuroimaging literature on human emotion. We compare the locationist approach (i.e., the hypothesis that discrete emotion categories consistently and specifically correspond to distinct brain regions) with the psychological constructionist approach (i.e., the hypothesis that discrete emotion categories are constructed of more general brain networks not specific to those categories) to better understand the brain basis of emotion. We review both locationist and psychological constructionist hypotheses of brain-emotion correspondence and report meta-analytic findings bearing on these hypotheses. Overall, we found little evidence that discrete emotion categories can be consistently and specifically localized to distinct brain regions. Instead, we found evidence that is consistent with a psychological constructionist approach to the mind: A set of interacting brain regions commonly involved in basic psychological operations of both an emotional and non-emotional nature are active during emotion experience and perception across a range of discrete emotion categories.

/pdf/the-brain-basis-of-emotion-a-meta-analytic-review-32zzrbb78z.pdf

The brain basis of emotion: A meta-analytic review

Sleep and the Price of Plasticity: From Synaptic and Cellular Homeostasis to Memory Consolidation and Integration

PET has the invaluable advantage of being intrinsically quantitative, enabling accurate measurements of tracer concentrations in vivo. In PET tumor imaging, indices characterizing tumor uptake, such as standardized uptake values, are becoming increasingly important, especially in the context of monitoring the response to therapy. However, when tracer uptake in small tumors is measured, large biases can be introduced by the partial-volume effect (PVE). The purposes of this article are to explain what PVE is and to describe its consequences in PET tumor imaging. The parameters on which PVE depends are reviewed. Actions that can be taken to reduce the errors attributable to PVE are described. Various PVE correction schemes are presented, and their applicability to PET tumor imaging is discussed.

https://jnm.snmjournals.org/content/jnumed/48/6/932.full.pdf

Partial-Volume Effect in PET Tumor Imaging

Regional cerebral blood flow throughout the sleep- wake cycle

Background: Activation of central serotonin (5-HT) 1A receptors, found in high density in brainstem raphe, hippocampus, and temporal neocortex, exerts an anticonvulsant effect in various experimental seizure models. To test the hypothesis that 5-HT 1A receptor binding is reduced in human epileptic foci, PET imaging was performed using the radioligand [ 18 F]trans-4-fluoro- N -2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]- N -(2-pyridyl)cyclohexanecarboxamide ([ 18 F]FCWAY), a selective 5-HT 1A receptor antagonist, in patients with temporal lobe epilepsy and normal controls. Methods: MRI and PET were performed using [ 15 O]water and [ 18 F]FCWAY in 10 controls and in 12 patients with temporal lobe epilepsy confirmed on ictal video-EEG; patients also underwent [ 18 F]fluorodeoxyglucose PET. Using quantitative PET image analysis, regional values were obtained for [ 18 F]FCWAY volume of distribution (V), cerebral blood flow (CBF), and glucose cerebral metabolic rate (CMRglc). Hippocampal volume (HV) was also measured with MRI. [ 18 F]FCWAY V PET and MR measures were compared within patients and controls using paired t -tests; grouped comparisons were made with two sample t -tests. Results: Lower [ 18 F]FCWAY V was found ipsilateral than contralateral to the epileptic focus in inferior medial (IMT) and lateral (ILT) temporal regions of patients (ILT 47.4 ± 6.1 vs 61.8 ± 6.1, p p 18 F]FCWAY V was 29% lower in raphe and 34% lower in the ipsilateral thalamic region of patients than controls. In ILT, mean [ 18 F]FCWAY V asymmetry index (AI) was significantly greater than mean CBF and mean CMRglc AI. Mean [ 18 F]FCWAY V AI in IMT was greater than mean HV AI, but the difference was not significant. Conclusion: These findings support the hypothesis of reduced serotonin receptor binding in temporal lobe epileptic foci.

PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy

Quantitative functional brain imaging with positron emission tomography

Objective: Succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal recessive disorder of GABA metabolism characterized by elevated levels of GABA and gamma-hydroxybutyric acid. Clinical findings include intellectual impairment, hypotonia, hyporeflexia, hallucinations, autistic behaviors, and seizures. Autoradiographic labeling and slice electrophysiology studies in the murine model demonstrate use-dependent downregulation of GABA(A) receptors. We studied GABA(A) receptor activity in human SSADH deficiency utilizing [ 11 C]-flumazenil (FMZ)-PET. Methods: FMZ binding was measured in 7 patients, 10 unaffected parents, and 8 healthy controls. Data analysis was performed using a reference region compartmental model, with time-activity curve from pons as the input function. Relative parametric binding potential ( BP ND ) was derived, with MRI-based pixel by pixel partial volume correction, in regions of interest drawn on coregistered MRI. Results: In amygdala, hippocampus, cerebellar vermis, frontal, parietal, and occipital cortex, patients with SSADH deficiency had significant reductions in FMZ BP ND compared to parents and controls. Mean cortical values were 6.96 ± 0.79 (controls), 6.89 ± 0.71 (parents), and 4.88 ± 0.77 (patients) ( F ratio 16.1; p Conclusions: Succinic semialdehyde dehydrogenase (SSADH) deficient patients show widespread reduction in BZPR binding on [ 11 C]-flumazenil-PET. Our results suggest that high endogenous brain GABA levels in SSADH deficiency downregulate GABA(A)-BZPR binding site availability. This finding suggests a potential mechanism for neurologic dysfunction in a serious neurodevelopmental disorder, and suggests that PET may be useful to translate studies in animal models to human disease.

/pdf/decreased-gaba-a-binding-on-fmz-pet-in-succinic-semialdehyde-31k5k9pmjx.pdf

Peter Herscovitch

Papers

Regional cerebral blood flow throughout the sleep- wake cycle

PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy

Quantitative functional brain imaging with positron emission tomography

Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency

Functional neuroanatomy of Tourette syndrome. Limbic-motor interactions studied with FDG PET.